A triazole-conjugated benzoxazone induces reactive oxygen species and promotes autophagic apoptosis in human lung cancer cells.

Abstract

Numerous approaches suggested that compounds with conjugated triazole moieties or benzoxazone pharmacores are effective to antagonize proliferation of human tumors. The current study reported that a synthetic triazole-conjugated benzoxazone, 4-((5-benzyl-1H-1,2,3-triazol-3-yl)-methyl)-7-methoxy-2H-benzo[b][1,4]-oxazin-3(4H)-one (BTO), inhibited growth rates of human non-small cell lung cancer cells. The cytotoxicity can be enhanced with increasing drug concentrations. More evidence supported that the induced reactive oxygen species lead to ultimate apoptotic cell death by recruiting autophagy. The mechanistic pathway as elucidated involved tumor suppressor p53 activation and LC3-1 conversion followed by PARP and procaspase-3 cleavage. Autophagy inhibition reverted apoptotic death and restored cell viabilities. BTO suppressed the development of A549 cell xenograft tumors by activating autophagy and apoptosis simultaneously. As an efficient tumor growth inhibitor with relatively small molecular weight, BTO is a viable addition to the existing list of lung cancer treatment.

• Authors: Chang-Heng Hsieh, Jing-Ping Wang, Chien-Chih Chiu, Chun-Yen Liu, Ching-Fa Yao, Kang Fang
• Journal: Apoptosis : an international journal on programmed cell death (Apoptosis) Vol. 23 Issue 1 Pg. 1-15 (01 2018) ISSN: 1573-675X [Electronic] Netherlands
• PMID: 29185084 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Benzoxazines
• Heterocyclic Compounds, 2-Ring
• MAP1LC3A protein, human
• Microtubule-Associated Proteins
• Reactive Oxygen Species
• Triazoles
• Tumor Suppressor Protein p53
• Poly(ADP-ribose) Polymerases
• Caspase 3

Topics

• A549 Cells
• Animals
• Antineoplastic Agents (chemical synthesis, pharmacology)
• Apoptosis (drug effects, genetics)
• Autophagy (drug effects, genetics)
• Benzoxazines (chemical synthesis, pharmacology)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, metabolism, pathology)
• Caspase 3 (genetics, metabolism)
• Cell Cycle (drug effects, genetics)
• Gene Expression Regulation, Neoplastic
• Heterocyclic Compounds, 2-Ring (chemical synthesis, pharmacology)
• Humans
• Injections, Subcutaneous
• Lung Neoplasms (drug therapy, genetics, metabolism, pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Microtubule-Associated Proteins (genetics, metabolism)
• Poly(ADP-ribose) Polymerases (genetics, metabolism)
• Reactive Oxygen Species (agonists, metabolism)
• Signal Transduction
• Triazoles (chemical synthesis, pharmacology)
• Tumor Suppressor Protein p53 (genetics, metabolism)
• Xenograft Model Antitumor Assays